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BackgroundThe outbreak of COVID-19 has profoundly influenced people’s lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown. ObjectiveThe aim of this paper was to study the association of COVID-19 pandemic–related impacts with health-related quality of life in patients with skin diseases. MethodsThis was a cross-sectional study among Chinese patients with skin diseases. A self-administered web-based questionnaire was distributed through social media. Demographic and clinical data and pandemic-related impacts (isolation status, income changes, and employment status) were collected. The main outcomes included perceived stress (Visual Analog Scale), symptoms of anxiety (Generalized Anxiety Disorder-7) and depression (9-Item Patient Health Questionnaire), quality of life (Dermatology Life Quality Index), and health utility mapping based on the EQ-5D-3L descriptive system. Multivariable logistic regression was used to investigate the associations. ResultsA total of 506 patients with skin diseases completed the survey. The mean age of the patients was 33.5 years (SD 14.0), and 217/506 patients (42.9%) were male. Among the 506 respondents, 128 (25.3%) were quarantined, 102 (20.2%) reported unemployment, and 317 (62.6%) reported decrease or loss of income since the pandemic. The pandemic-related impacts were significantly associated with impaired mental well-being and quality of life with different effects. Unemployment and complete loss of income were associated with the highest risks of adverse outcomes, with increases of 110% to 162% in the prevalence of anxiety, depression, and impaired quality of life. ConclusionsIsolation, income loss, and unemployment are associated with impaired health-related quality of life in patients with skin diseases during the COVID-19 pandemic.

Compared to the traditional Intensity Modulation and Direct Detection (IM/DD) system, the coherent system offers higher capacity and power budget, better meeting the needs of high-capacity Passive Optical Network (PON). In recent years, the application of coherent technology in PON to better support future high-bandwidth services has become a hot research topic. This article summarizes the research progress in coherent PON technology from four aspects: system architecture, coherent simplification, uplink burst-mode detection, and flexible PON. In addition, it proposes laser-shared uplink and downlink Filter Bank Multi-Carrier (FBMC)-PON and Semiconductor Optical Amplifier (SOA) current-adjusted flexible PON schemes.

Small molecule inhibitors of the bromodomain and extraterminal domain (BET) family proteins have emerged as promising options not only for the treatment of multiple cancers but also for disturbing the process of sperm maturation with potential for use as viable contraceptive targets. In this study, we find that the BET family inhibitor NHWD870 and BRDT can bind well in vitro through bioinformatics software prediction and protein binding inhibition experiments. NHWD870 can produce a good contraceptive effect through animal experiments in vivo, and the fertility can be restored to normal after drug withdrawal. Transcriptomics and proteomics results suggest that NHWD870 affects pathways related to spermatogenesis and maturation, further contributing to the male infertility phenotype. Our results show that NHWD870 can induce a complete and reversible contraceptive effect in mice, which is stronger than that of JQ1 and its synthesized derivatives. This study is expected to eventually lead to clinical trials.

Author(s): Shang-Min Zhang [sup.1] , Wesley L. Cai [sup.1] [sup.12] , Xiaoni Liu [sup.1] [sup.2] , Durga Thakral [sup.2] , Jiesi Luo [sup.3] [sup.4] , Lok Hei Chan [sup.1] , [...], Tumours use various strategies to evade immune surveillance.sup.1,2. Immunotherapies targeting tumour immune evasion such as immune checkpoint blockade have shown considerable efficacy on multiple cancers.sup.3,4 but are ineffective for most patients due to primary or acquired resistance.sup.5-7. Recent studies showed that some epigenetic regulators suppress anti-tumour immunity.sup.2,8-12, suggesting that epigenetic therapies could boost anti-tumour immune responses and overcome resistance to current immunotherapies. Here we show that, in mouse melanoma models, depletion of KDM5B--an H3K4 demethylase that is critical for melanoma maintenance and drug resistance.sup.13-15--induces robust adaptive immune responses and enhances responses to immune checkpoint blockade. Mechanistically, KDM5B recruits the H3K9 methyltransferase SETDB1 to repress endogenous retroelements such as MMVL30 in a demethylase-independent manner. Derepression of these retroelements activates cytosolic RNA-sensing and DNA-sensing pathways and the subsequent type-I interferon response, leading to tumour rejection and induction of immune memory. Our results demonstrate that KDM5B suppresses anti-tumour immunity by epigenetic silencing of retroelements. We therefore reveal roles of KDM5B in heterochromatin regulation and immune evasion in melanoma, opening new paths for the development of KDM5B-targeting and SETDB1-targeting therapies to enhance tumour immunogenicity and overcome immunotherapy resistance. KDM5B recruits SETDB1 to repress endogenous retroelements such as MMVL30, suppressing anti-tumour immunity, and the depletion of KDM5B induces a robust adaptive immune response and enhances the response to immune checkpoint blockade.

Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4+ epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor‐associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1‐CD44 and CD155‐CD226 ligand‐receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis. [ABSTRACT FROM AUTHOR]